HIV surrogate markers weighed
Article Abstract:
New drugs must be shown to be safe and effective in laboratory tests before being administered to humans. These tests must be accurate and, in the case of the urgent need for drugs to fight AIDS and the AIDS virus, the testing process needs to be expedited. Many people advocate that drugs for treating AIDS be approved quickly, even without complete testing, because the need outweighs possible risks. Presently, only zidovudine (AZT) is licensed to treat AIDS. One way to speed up the testing process is by identifying surrogate markers that indicate an effective drug response. Surrogate markers are the measurements that are analyzed to determine if the drug being tested is effective against the target disease. One study advocates that CD4 counts and serum beta2-microglobulin measurements are the best markers for testing AIDS drugs. CD4 counts reflect the number of CD4 lymphocytes (cells of the immune system) in a given blood volume. CD4 cells are destroyed by AIDS. Most patients with AIDS die once their CD4 levels drop below 50 cubic millimeters, and researchers believe that a drug that keeps CD4 levels above this ceiling are effective in fighting AIDS. Other research has shown that some drugs can be effective against AIDS without affecting CD4 counts. Recent studies have shown that the effectiveness of AZT can not completely be accounted for by increasing CD4 counts. Research concerning the new drug inosine pranobex has shown it to be effective against AIDS without increasing the number of CD4 lymphocytes; it has been suggested that an X (unknown) factor is involved. Inosine pranobex has not been approved in the US because of the lack of both concrete studies and knowledge of how it works. CD4 counts seem to vary by ethnic and sex differences, and can even vary greatly within an individual. Problems in obtaining accurate CD4 counts might account for some of these discrepancies. Despite these problems, CD4 counts seem to be reasonably safe as an effective surrogate marker in evaluating drugs to treat AIDS. A task force, including the FDA, National Institute of Allergy and Infectious Diseases, and National Cancer Institute, will be working on developing guidelines for surrogate markers. (Consumer Summary produced by Reliance Medical Information, Inc.)
Publication Name: JAMA, The Journal of the American Medical Association
Subject: Health
ISSN: 0098-7484
Year: 1991
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FDA 'pushing envelope' on AIDS drug
Article Abstract:
David Kessler, commissioner of the Food and Drug Administration, announced what he called a milestone in the process by which drugs are reviewed and voted for approval. The drug didanosine (DDI), developed to fight the AIDS virus, was recommended for approval by an outside committee of experts only three and one half months after the manufacturer applied to the government. While some think that speeding the approval process for such drugs is important, others believe that dangerous precedents are being set. The antiviral drug will potentially be useful in treating patients for whom zidovudine (AZT) is no longer effective. Proponents of rapid approval say that since no other drug is available for slowing the inevitably fatal progression of AIDS, there is compelling reason to approve and begin to use the drug in treatment. However, the evidence for its efficacy comes only from laboratory data such as CD4 cell counts and levels of p24 viral antigen in the blood. While it seems clear that treatment with didanosine slightly increases CD4 cells, generally regarded as a good sign, there is not yet any evidence indicating that patients receiving the drug will have a reduction in opportunistic infections or live longer. Furthermore, if the drug is approved, then patients who are at present participating in experimental evaluation of the drug may opt to leave the experiment for treatment; the result may be that early approval may mean delayed knowledge of the drug's true value. The approval of the drug may prompt other pharmaceutical firms to also attempt to rush drugs through the approval process before research is complete. Some physicians have raised the point that most of the data comes from white gay men, despite the fact that intravenous drug users, often minority members, and women are now the fastest growing groups of AIDS patients. There is some indication that didanosine may impair liver function. Since drug abusers often already have impaired liver function, it is far from certain that the data obtained on white gay men are applicable to other groups of AIDS patients. (Consumer Summary produced by Reliance Medical Information, Inc.)
Publication Name: JAMA, The Journal of the American Medical Association
Subject: Health
ISSN: 0098-7484
Year: 1991
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Surrogate markers of disease studied as means of determining AIDS drugs' effectiveness
Article Abstract:
Dideoxycytidine (ddC) and didanosine (ddI) are related to the drug zidovudine, which is the only drug currently approved for treating AIDS. The new zidovudine analogs are currently being tested for use in the treatment of AIDS. However, the value of using certain measurements, such as the number of CD4 cells, a type of immune cell, to determine the effectiveness of a drug against AIDS, has not been established. All three agents prevent the replication of the human immunodeficiency virus (HIV), which causes AIDS, and peripheral nerve disease as well. Unlike zidovudine, ddI and ddC do not suppress bone marrow function. Although ddI can cause pancreatitis (inflammation of the pancreas), this side effect is manageable. The combined use of ddI and ddC is more effective against HIV infection than their use individually, and is associated with fewer side effects and diminished viral resistance. AIDS activists are pushing for the approval of ddI and ddC by the Food and Drug Administration (FDA) by January 1, 1991. A committee was appointed by the federal government to review the procedures for approving new drugs for treating cancer and AIDS. They suggested that the requirement for a drug to prolong life should not be considered essential for FDA approval if the new agent improves CD4 counts and function of the patient and decreases the incidence of AIDS-related opportunistic infections. Patients with AIDS are willing to accept the risks associated with early approval of a new drug, and AIDS activist groups point to a moral obligation to provide new options for patients. If these new agents are approved for use in treating AIDS, their costs will be covered by appropriate third-party payers. Although unrestricted licensing of these new drugs is not recommended, they could be prescribed for patients who cannot tolerate or do not respond to zidovudine. (Consumer Summary produced by Reliance Medical Information, Inc.)
Publication Name: JAMA, The Journal of the American Medical Association
Subject: Health
ISSN: 0098-7484
Year: 1990
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